Most Genetic Epidemiology Branch investigations evaluate the contributions of host susceptibility and environmental exposure in the development of cancer. In family studies, melanoma cases from families with CDKN2A (p16) mutations were more likely than their unaffected relatives to have a CDKN2A mutation, dysplastic nevi, increased total number of nevi, abnormal mole pattern, pale or fair complexion and solar injury. Even after adjustment for CDKN2A mutation and age, these same factors each showed significant associations with melanoma. A new study of familial chordoma, a rare, low-grade, malignant bone tumor derived from remnants of the notochord, was initiated. A large family with nine affected individuals in three generations was clinically and radiologically evaluated. A genome-wide scan to localize a chordoma gene is underway. A gene for familial eosinophilia was mapped to a small region of chromosome 5q in a large five-generation family with 19 affected and 33 unaffected members. Clinical evaluation of the family revealed, as expected, significantly higher white cell and absolute eosinophil counts as well as lower red cell counts, in affected patients compared to their unaffected relatives or spouses. Clinical examination of a cohort of 105 patients with the nevoid basal cell carcinoma syndrome (NBCC) showed the frequencies of the various manifestations of the syndrome. Eighty percent of whites and 38% of African-Americans had at least one basal cell carcinoma with a median of 8 and 2, respectively. Jaw cysts occurred in 74% of patients with a median of 3 cysts. The most common finding was palm and/or sole pits in 87% of patients. Other tumors found in the syndrome included ovarian fibromas and medulloblastomas. A rare case of NBCC in an African-American child who was initially diagnosed with medulloblastoma was reported. The findings illustrate complex gene-environment interaction, represented by the development of numerous basal cell carcinomas in areas irradiated for medulloblastoma, in a patient with increased skin pigmentation, presumably protected against ultraviolet radiation but not ionizing radiation.